Central nervous system vasculitis associated with hepatitis C virus infection: a brain MRI-supported diagnosis.

BACKGROUND: The Hepatitis C virus (HCV) infection is associated with various extrahepatic manifestations, being the Central Nervous System (CNS) rarely involved. CASE REPORT: We report a case of a 54 year-old black man with arterial hypertension who presented with progressively worsening headaches, apathy, somnolence and left hemiparesis. Brain MRI showed an acute ischemic lesion in the left anterior cerebral artery (ACA) and an old ischemic infarct in the right ACA territory. Brain MRI with gadolinium revealed mural thickening and contrast enhancement of the A1 and A2 segments of the ACAs, of the middle and distal basilar artery and of the P1 segment of the left posterior cerebral artery, suggesting active vasculitis. Digital angiography confirmed those irregularities and stenosis. Laboratory evaluation revealed ESR (73 mm/h), transaminase elevation, elevated HCV viral load genotype 2, positive IGRA, negative cryoglobulins, CSF protein elevation with oligoclonal bands (mirror pattern) and no pleocytosis; investigation excluded other infectious causes. Pegylated interferon alpha-2a and ribavirin, corticotherapy and tuberculosis prophylaxis were started with clinical and imagiological improvement. CONCLUSION: The typical inflammation signs of the vascular wall demonstrated by the gadolinium-enhanced MRI strengthened the hypothesis of CNS vasculitis. The association with HCV infection is rare but should be investigated once specific therapeutic is required.

Learning orthography in adulthood: a magnetoencephalographic study.

Previous work demonstrated that there were differences between literate and comparable illiterate adult subjects. These differences were found in the performance on several tests and on patterns of activation on PET and fMRI. In the present study subjects that learned to read and to write in adulthood (being previously completely illiterate) were compared to controls, that is subjects that learned at school at the proper age. Magnetoencephalography was done while subjects were reading words. Results showed that, although the reading performance was the same in both groups while performing the task, the pattern of source distribution was different between groups. There were more late sources in right temporo-parietal areas of late literates compared to controls and more late sources in left inferior frontal cortex in control subjects. It is concluded that learning to read in adulthood is a process supported by different brain structures from the ones used when learning occurs at the proper age. This may suggest that the same task can be similarly performed by relying on diverse functional brain anatomic networks.

Formal schooling influences two- but not three-dimensional naming skills.

The modulatory influence of literacy on the cognitive system of the human brain has been indicated in behavioral, neuroanatomic, and functional neuroimaging studies. In this study we explored the functional consequences of formal education and the acquisition of an alphabetic written language on two- and three-dimensional visual naming. The results show that illiterate subjects perform significantly worse on immediate naming of two-dimensional representations of common everyday objects compared to literate subjects, both in terms of accuracy and reaction times. In contrast, there was no significant difference when the subjects named the corresponding real objects. The results suggest that formal education and learning to read and to write modulate the cognitive process involved in processing two- but not three-dimensional representations of common everyday objects. Both the results of the reaction time and the error pattern analyses can be interpreted as indicating that the major influence of literacy affects the visual system or the interaction between the visual and the language systems. We suggest that the visual system in a wide sense and/or the interface between the visual and the language system are differently formatted in literate and illiterate subjects. In other words, we hypothesize that the pattern of interactions in the functional-anatomical networks subserving visual naming, that is, the interactions within and between the visual and language processing networks, differ in literate and illiterate subjects.

Language processing modulated by literacy: a network analysis of verbal repetition in literate and illiterate subjects.

Previous behavioral and functional neuroimaging data indicate that certain aspects of phonological processing may not be acquired spontaneously, but are modulated by learning an alphabetic written language, that is, learning to read and write. It appears that learning an alphabetic written language modifies the auditory-verbal (spoken) language processing competence in a nontrivial way. We have previously suggested, based on behavioral and functional neuroimaging data, that auditory-verbal and written language interact not only during certain language tasks, but that learning and developing alphabetic written language capacities significantly modulates the spoken language system. Specifically, the acquisition of alphabetic orthographic knowledge has a modulatory influence on sublexical phonological processing and the awareness of sublexical phonological structure. We have suggested that developing an orthographic representation system for an alphabetic written language, and integrating a phoneme-grapheme correspondence with an existing infrastructure for auditory-verbal language processing, will result in a modified language network. Specifically, we suggest that the parallel interactive processing characteristics of the underlying language-processing brain network differ in literate and illiterate subjects. Therefore, the pattern of interactions between the regions of a suitably defined large-scale functional-anatomical network for language processing will differ between literate and illiterate subjects during certain language tasks. In order to investigate this hypothesis further, we analyzed the observed covariance structure in a PET data set from a simple auditory-verbal repetition paradigm in literate and illiterate subjects, with a network approach based on structural equation modeling (SEM). Based on a simple network model for language processing, the results of the present network analysis indicate that the network interactions during word and pseudoword repetition in the illiterate group differ, while there were no significant differences in the literate group. The differences between the two tasks in the illiterate group may reflect differences in attentional modulation of the language network, executive aspects of verbal working memory and the articulatory organization of verbal output. There were no significant differences between the literate and illiterate group during word repetition. In contrast, the network interactions differed between the literate and illiterate group during pseudoword repetition. In addition to differences similar to those observed in the illiterate group between word and pseudoword repetition, there were differences related to the interactions of the phonological loop between the groups. In particular, these differences related to the interaction between Broca's area and the inferior parietal cortex as well as the posterior-midinsula bridge between Wernicke's and Broca's area. In conclusion, the results of this network analysis are consistent with our previously presented results and support the hypothesis that learning to read and write during childhood influences the functional architecture of the adult human brain. In particular, the basic auditory-verbal language network in the human brain is modified as a consequence of acquiring orthographic language skills.

Effective auditory-verbal encoding activates the left prefrontal and the medial temporal lobes: A generalization to illiterate subjects.

Recent event-related FMRI studies indicate that the prefrontal (PFC) and the medial temporal lobe (MTL) regions are more active during effective encoding than during ineffective encoding. The within-subject design and the use of well-educated young college students in these studies makes it important to replicate these results in other study populations. In this PET study, we used an auditory word-pair association cued-recall paradigm and investigated a group of healthy upper middle-aged/older illiterate women. We observed a positive correlation between cued-recall success and the regional cerebral blood flow of the left inferior PFC (BA 47) and the MTLs. Specifically, we used the cued-recall success as a covariate in a general linear model and the results confirmed that the left inferior PFC and the MTL are more active during effective encoding than during ineffective encoding. These effects were observed during encoding of both semantically and phonologically related word pairs, indicating that these effects are robust in the studied population, that is, reproducible within group. These results generalize the results of Brewer et al. (1998, Science 281, 1185-1187) and Wagner et al. (1998, Science 281, 1188-1191) to an upper middle aged/older illiterate population. In addition, the present study indicates that effective relational encoding correlates positively with the activity of the anterior medial temporal lobe regions.

Influence of learning to read and write on the morphology of the corpus callosum.

Variations in the individual anatomy of the corpus callosum have been reported in several conditions. There seem to be genetic influencing factors, but it is impossible to rule out some environmental ones. This study focuses on the question of the environmental factors, using formal learning to read and write as the main difference in the groups to be compared. Based on magnetic resonance imaging sagital images, the contour of the corpus callosum (CC) of 41 carefully selected women (18 illiterate and 23 literate) was digitized. The comparison between the two groups showed a small difference in the region of the CC where parietal fibres are thought to cross. This region is thinner in illiterate subjects. As illiteracy in this group is the result of social constraints, and the two groups that were compared are well matched for other cultural and pragmatic aspects than literacy, the results are interpreted as showing the possible influence of formal learning to read and write, on the biological development of the brain.

Problems of patients with chronic aphasia: different perspectives of husbands and wives?

During the early phase following stroke, patients with aphasia and their families are totally involved in the rehabilitation programme, but later, in the chronic phase, after discharge, the family generally has no support and many problems may arise or become more acute and provoke disturbances in this system. The patients with aphasia and their spouses may feel the situation differently according to their own characteristics, including gender. The present study includes 55 spouses of patients with chronic aphasia and 37 controls (spouses of subjects without physical or cognitive impairments) who filled out a questionnaire concerning their respective spouses (European Brain Injury Questionnaire--EBIQ) and some aspects about themselves. It was concluded, from the opinions expressed by the spouses of patients with chronic aphasia that they have problems in several domains not only related to communication or physical impairments. The opinions of husbands and wives of patients with aphasia, but not of the controls, were different, with more references to behaviour changes in women with aphasia. Spouses' responses also show important changes in their own lives. These results stress the importance of adequate attention to the long-term psychosocial problems of patients and relatives.

Spontaneous complaints of long-term traumatic brain injured subjects and their close relatives.

Long-term consequences of head injury for patients and families are not well known, given the complexity of variables that have to be studied. Subject's self-experience is one of these less studied aspects. The purpose of this study is to examine the spontaneous complaints of long-term brain injured adult subjects to be compared to the impression of their relatives. A total of 48 chronic head trauma subjects were studied more than 6 years after injury together with a relative, usually a mother or wife. At the beginning of the interview the participants were asked to freely refer their present complaints. In general, relatives referred more complaints about the injured subjects than the injured subjects referred about themselves. This occurred in several domains: somatic, physical, cognitive, and behavioural. Memory problems were highly reported by both groups. Somatic complaints were more frequently reported by patients and behavioural problems were more often reported by relatives. Mothers and wives had different profiles or responses. Mothers' opinions were identical to those of their TBI sons in all domains. These different results must be taken into consideration so that the real needs of patients and relatives can be addressed.

The illiterate brain. Learning to read and write during childhood influences the functional organization of the adult brain.

Learning a specific skill during childhood may partly determine the functional organization of the adult brain. This hypothesis led us to study oral language processing in illiterate subjects who, for social reasons, had never entered school and had no knowledge of reading or writing. In a brain activation study using PET and statistical parametric mapping, we compared word and pseudoword repetition in literate and illiterate subjects. Our study confirms behavioural evidence of different phonological processing in illiterate subjects. During repetition of real words, the two groups performed similarly and activated similar areas of the brain. In contrast, illiterate subjects had more difficulty repeating pseudowords correctly and did not activate the same neural structures as literates. These results are consistent with the hypothesis that learning the written form of language (orthography) interacts with the function of oral language. Our results indicate that learning to read and write during childhood influences the functional organization of the adult human brain.

DYSBOT: a single-blind, randomized parallel study to determine whether any differences can be detected in the efficacy and tolerability of two formulations of botulinum toxin type A--Dysport and Botox--assuming a ratio of 4:1.

BACKGROUND: Elston and Russell discovered a difference in the biological potency of the English formulation of botulinum toxin type A or BTX-A (Dysport) and the American formulation (Botox). Potency of both is expressed in LD50 mouse units, but because of assay differences, these units are not equivalent. Since the first warning by Quinn and Hallet on the clinical importance of this issue, it has been impossible to reach a consensus on the conversion factor for the potency of these formulations. OBJECTIVE: To test the hypothesis that the conversion factor for the clinical potency of Dysport to Botox is approximately 4:1. DYSBOT is an acronym that results from adding "DYS" from Dysport with "BOT" from Botox. DESIGN: A single-blind, randomized, parallel comparison. A total of 91 patients with blepharospasm or hemifacial spasm were randomized to treatment with Dysport or Botox using a fixed potency ratio of 4:1. Clinical evaluations: The patients were evaluated at baseline (day of the treatment). 1 month after treatment, and whenever the effect was judged to be fading. Objective and functional rating scales were used as quantitative measures of the change in clinical status. Adverse reactions were collected using a systematic questionnaire. RESULTS: Using this ratio between products, both Dysport and Botox groups produced similar clinical efficacy and tolerability. For patients showing a positive response without the need of a booster, the duration of effect was 13.3 +/- 5.9 weeks for the Dysport group and 11.2 +/- 5.8 weeks for the Botox group. Of 48 patients, 11 (23%) needed booster treatment in the Dysport group compared with five (12%) of 43 in Botox group. Adverse events were noted in 24 (50%) of 48 patients in the Dysport group and 20 (47%) of 43 of the Botox-treated group. CONCLUSIONS: Using a 4:1 conversion ratio for Dysport and Botox, similar results were obtained for the two treatments in an appropriately powered study, suggesting that this conversion factor is a good estimate of their comparative clinical potencies.

Illiteracy: a cause for biased cognitive development.

Learning to read and write generates new rules within the language processing systems. These new rules significantly change the manner in which some operations are performed. This finding was studied, by comparing the performance of literate and illiterate persons in several tasks. It was found that illiterate individuals (1) had difficulties in repeating pseudowords, (2) were worse at memorizing pairs of phonologically related words compared to pairs of semantically related words, and (3) were unable to generate words according to a formal criterion. Illiterate persons use strategies that are good for semantic processing, but inadequate for phonological analysis, while literate individuals are able to use several parallel running strategies.

Subjective experience in brain-injured patients and their close relatives: a European Brain Injury Questionnaire study.

Results are reported from an international project the aim of which has been to develop and validate a wide-ranging questionnaire suitable for administration to brain-injured patients and their relatives. A self-report questionnaire concerning subjective experience of cognitive, emotional and social difficulties (The European Brain Injury Questionnaire, EBIQ) was administered to a group of 905 brain-injured patients, and close relatives to these competed a parallel version of the questionnaire concerning the brain-injured person. The sample was drawn from seven European countries together with Brazil. The same questionnaire was also administered to a group of 203-non-brain-injured controls, similarly in self-report and relative-report versions. Scales relating to eight specific areas of functioning, together with a global scale, are derived from the questionnaire and their internal reliability was estimated in the present data. Analyses of the 63 items of the questionnaire showed consistently greater levels of problems for the brain-injured group, especially as indicated by relatives. This pattern was substantially replicated among the nine scales. The scales discriminated well between stroke patients and those who had suffered a traumatic brain injury. There was also a tendency for reported problems to be greater for patients who were surveyed later post-injury (> or = 19 months) rather than earlier. Comparison of sets of controls derived from two countries (France and Brazil) showed small but important differences. It is concluded that the questionnaire has an acceptable reliability and validity, but that it will be necessary to obtain culturally relevant non-brain-injured control data when employing it in different countries.

Botulinum toxin type A for the treatment of arm and hand spasticity in stroke patients.

BACKGROUND: Focal spasticity can be a major drawback in the rehabilitation of stroke patients. Previous studies suggest a beneficial effect for botulinum toxin A (BTX-A) for relief of spasticity. OBJECTIVE: To evaluate the safety and efficacy of BTX-A in the treatment of spasticity in a homogeneous group of stroke patients. METHODS: In this phase III open label trial 19 stroke patients stable for at least six months were enrolled (mean age 53.1 (SD 3.27) years; range 26-72). There were 16 males and 4 females. ASSESSMENTS: Clinical (Ashworth spasticity rating scale, scores for joint mobility, pain and frequency of spasms, Frenchay arm test (FAT)) and subjective (semi-quantitative rating scale filled out by the patient). Only hand and finger flexors were injected. The maximum dosage was 150 U BOTOX (25 U/muscle), the mean dosage was 92.1 +/- 31.6 U BOTOX. RESULTS: Ashworth rating scale and joint mobility scores improved from a median value of 2 at baseline to a median value of 1 one month after treatment, FAT scores also improved from a median value of 0 at baseline to a median value of 1 one month after treatment (Kruskall-Wallis test p < 0.01). Two-thirds of the patients rated their functional improvement as none or mild. CONCLUSIONS: Our study confirmed that BTX-A has an anti-spastic effect but its functional impact needs further evaluation.

Aphasia following right hemisphere lesion in a woman with left hemisphere injury in childhood.

The case of a 56-year-old woman who became aphasic following a right temporoparietal lesion is reported. At the age of 2, this woman had an acute infantile hemiplegia on the right side of the body and it was reported by relatives that a deterioration of language was also noted. There was a slow recovery of these deficits and she was considered as having normal language only at age 7. Although it is difficult to be sure about the hand preference of the patient before the stroke at age 2, the relatives were quite positive saying, that she previously preferred the right hand and that she became left handed. The CT scan showed an old left frontal ischemic lesion and a recent right temporoparietal lesion. This case illustrates the ability of the right hemisphere to take over functions of the left when a left lesion occurs in early stages of language acquisition. Although this is an accepted model for recovery, this is the only case in the literature with a documented early focal lesion of the left hemisphere. Other evidence comes from studies performed in populations where severe epilepsy may contribute to particular functional organization.

Atypical dominance for language in developmental dysphasia.

The authors report an association between developmental language disorder and acquired aphasia in a 13-year-old right-handed boy. Acquired aphasia was caused by a right-frontal abscess (crossed aphasia). It was non-fluent, with a disorder of auditory comprehension, an unusual feature of prerolandic lesions. This case shows that developmental language impairment can be associated not only with an atypical cerebral dominance, but also with unusual patterns of intrahemispheric specialization. The rapid and complete recovery of this boy's aphasia suggests that the cerebral plasticity for acquired lesions can be normal in such cases.

The response of "de novo" Parkinson's disease patients to bromocriptine in a "low and slow" regimen is predictive for prognosis.

It is possible that Bromocriptine only determines a complete antiparkinson effect in a subset of P.D. patients that have a good dopaminergic reserve. Our study intent to demonstrate that a good short-term response to Bromocriptine used in a "low and slow" regimen is a marker of long term good prognosis. We studied a series of 36 sequential "de novo" P.D. patients treated with Bromocriptine in a "low and slow" regimen. The principal end-point was the introduction of Levodopa. "Good prognosis" was defined as no need of Levodopa until five years of follow-up. An improvement greater than 33% in the Columbia rating scale, at the 6th month of treatment, was the cut-off point to decide that a patient had a good short term response to Bromocriptine. Nine patients fulfilled the criteria for being good short term responders. Multiple regression analysis showed that this outcome could not be predicted by the clinical characteristics of the patients at admission. The sensitivity and the specificity of the short term response to Bromocriptine to predict a good prognosis were 70% and 90.5% respectively. We conclude that Bromocriptine in monotherapy is an efficient antiparkinson agent in 1/3 of "de novo" P.D. patients and good short term response to Bromocriptine is an acceptable marker for a good prognosis. Therefore it is possible that the response to Bromocriptine is a discriminator for a subset of P.D. patients in the early phases of the disease.